Anion conducting polymers (ACPs) are essential materials for alkaline electrochemical energy technology such as anion-exchange membrane fuel cells (AEMFC) and water electrolysers (AEMWE). The aforementioned polymers are promising alternatives for...
Hypoxia and NOTCH signaling have been reported to be associated with the self-renewal and drug resistance of cancer stem cells (CSCs). However, the molecular mechanisms by which hypoxia and NOTCH signaling stimulate the self-renewal and drug resistance of ovarian CSCs are poorly understood. In the present study, we identified SOX2 as a key transcription factor for CSC-like characteristics in the downstream of hypoxia-induced NOTCH signaling in epithelial ovarian cancer cells. Hypoxic treatment or overexpression of intracellular domain of NOTCH1 (NICD1) in ovarian cancer cells increased sphere formation, drug resistance, and expression of CSC-associated genes such as SOX2, ALDH, and ABC transporters. Hypoxic treatment increased the expression of NICD1, and hypoxic treatment or NICD1 overexpression increased SOX2 promoter activity, which was inhibited by deletion of HIF-1 or CSL binding sites. Furthermore, DAPT treatment decreased the effect of hypoxic treatment, and SOX2 knockdown decreased the effect of hypoxic treatment and NICD overexpression on sphere formation and drug resistance in established ovarian cancer cell lines and primary ovarian cancer cells. These results suggest that hypoxia-NOTCH1-SOX2 signaling axis is important for activation of ovarian CSCs, which may provide a novel opportunity for developing therapeutics to eradicate CSCs in ovarian cancer patients.
In proton therapy dosimetry, a fiber-optic radiation sensor incorporating a scintillator must undergo complicated correction processes due to the quenching effect of the scintillator. To overcome the drawbacks of the fiber-optic radiation sensor, we proposed an innovative method using the Cerenkov radiation generated in plastic optical fibers. In this study, we fabricated a fiber-optic Cerenkov radiation sensor without an organic scintillator to measure Cerenkov radiation induced by therapeutic proton beams. Bragg peaks and spread-out Bragg peaks of proton beams were measured using the fiber-optic Cerenkov radiation sensor and the results were compared with those of an ionization chamber and a fiber-optic radiation sensor incorporating an organic scintillator. From the results, we could obtain the Bragg peak and the spread-out Bragg peak of proton beams without quenching effects induced by the scintillator, and these results were in good agreement with those of the ionization chamber. We also measured the Cerenkov radiation generated from the fiber-optic Cerenkov radiation sensor as a function of the dose rate of the proton beam.
Objective: To examine the relationship between types and locations of mutations of the enzyme α-galactosidase (Gal) A in Fabry disease and the response to the pharmacological chaperone 1-deoxygalactonojirimycin (DGJ). Methods:T-cells grown from normal individuals or from patients with Fabry disease were tested for response to treatment with DGJ by increased activity of α-Gal A.Results: Cells from normal controls responded with a 28% increase in α-Gal A activity whereas response in Fabry individuals was mutation dependent ranging from no increase to fully normal activity. Nine truncation mutations (all non-responsive) and 31 missense mutations were tested. Three groups of missense mutations were categorized: responders with activity more than 25% of normal, non-responders, with less than 7% and an intermediate response group. In normal cells and in responders an increase in the mature lysosomal form of α-Gal A was observed after DGJ treatment. Non-responders showed little or no protein with or without DGJ. The intermediate response group showed an increase in band intensity but incomplete processing of the enzyme to the mature form. Conclusions:Mapping the missense mutations to the structure of α-Gal A identified several factors that may influence response. Mutations in regions that are not in α-helix or β-sheets, nor involved in disulfide bonds nor with an identified functional or structural role were more likely to respond. However, predictability is not precise and testing each mutation for response to pharmacological chaperone therapy is necessary for Fabry disease and related lysosomal storage disorders.
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